Squalene synthetase is a microsomal enzyme which catalyzes the reductive dimerization of two molecules of farnesyl pyrophosphate (FPP) in the presence of nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) to form squalene (Poulter, C.D.; Rilling, H.C., in "Biosynthesis of Isoprenoid Compounds", Vol. I, Chapter 8, pp. 413-441, J. Wiley and Sons, 1981, and references therein). This enzyme is the first committed step of the de novo cholesterol biosynthetic pathway. The selective inhibition of this step should allow the essential pathways to isopentenyl tRNA, ubiquinone, and dolichol to proceed unimpeded. Squalene synthetase along with HMG-CoA reductase have been shown to be down-regulated by receptor mediated LDL uptake (Faust, J.R.; Goldstein, .L.; Brown, M.S. Proc. Nat. Acad. Sci. U.S.A. 1979, 76, 5018-5022), lending credence to the proposal that inhibiting squalene synthetase will lead to an up-regulation of LDL receptor levels, as has been demonstrated for HMG-CoA reductase, and thus ultimately should be useful for the treatment and prevention of hypercholesterolemia and atherosclerosis.
U.S. Pat. No. 3,313,735 to McCune disclose shampoo compositions which include phosphono compounds of the formulae ##STR2## wherein R is an alkyl radical containing 6 to 18 carbons, X is H or methyl, Z is OH, COOM and PO.sub.3 M.sub.2, and M is H, Na, K, ammonium, and low molecular weight substituted ammonium.
B. Eriksson et al, Biochimica et Biophysica Acta 1982, 696, 115-123 and Proc. Int. Congr. Chemother. 13th 1982, 6, 114/29-114/32 disclose inhibitors of DNA polymerases of cytomegalovirus and herpes simplex virus having the formula ##STR3## wherein R is H, CH.sub.3, CH.sub.2 CH.sub.3, (CH.sub.2).sub.2 CH.sub.3, (CH.sub.2).sub.8 CH.sub.3, phenyl or OH.
B. Lofgren et al, Antiviral Research 1989, 12, 301-310 discloses inhibitors of the DNA polymerase of hepadnaviruses having the structure ##STR4## wherein R is OH, (CH.sub.2).sub.4 CH.sub.3, (CH.sub.2).sub.6 CH.sub.3, (CH.sub.2).sub.8 CH.sub.3, (CH.sub.2).sub.10 CH.sub.3, ##STR5##
A. Widell et al, Antiviral Research 1986, 6, 103-112, discloses inhibitors of hepatitis A virus having the structure ##STR6##
E.W. Maurer et al, J. Am. Oil Chemists' Soc., 1964, 41(3), 206-208, discloses .alpha.-phosphono fatty acids, esters and their salts having the structure ##STR7## wherein R is (CH.sub.2).sub.6 CH.sub.3 to (CH.sub.2).sub.15 CH.sub.3 and R.sup.a is H or methyl, isopropyl or aryl esters (containing 14 to 19 carbons in total).
B. Ackerman et al, J. Am. Chem. Soc. 1957, 79, 6524-6526 discloses triethyl esters of .alpha.-phosphono acid of the structure ##STR8## wherein R is C.sub.2 H.sub.5 to C.sub.16 H.sub.33.
Y. Okamoto et al, Kogyo Kagaku Zasshi 1966, 69(9), 1871-1875, disclose surface-active agents and detergents having the formula ##STR9## wherein n is 9, 11, 13 or 15.